New form of intellectual disability discovered -- TORONTO, April 27, 2012

New form of intellectual disability discovered

TORONTO, April 27, 2012 /PRNewswire/ - Researchers at the Centre for Addiction and Mental Health (CAMH) led a study discovering a gene for a new form of intellectual
disability, as well as how it likely affects cognitive development by
disrupting neuron functioning.

CAMH Senior Scientist Dr. John Vincent and his team found a mutation in the gene NSUN2among three sisters with intellectual disability, a finding to be
published in the May issue of the American Journal of Human Genetics.

The discovery was made after mapping genes in a Pakistani family, in
which three of seven siblings had intellectual disability as well as
muscle weakness and walking difficulties, says Dr. Vincent, who heads
the Molecular Neuropsychiatry and Development Laboratory in the Campbell Family Mental Health Research Institute at CAMH.

Intellectual disability is a condition in which individuals have
limitations in their mental abilities and in functioning in daily life.
It affects one to three per cent of the population, and is often caused
by genetic mutations.

Another study in the same journal, submitted together with the CAMH-led
research, also identified NSUN2 gene mutations in Iranian and Kurdish
families with intellectual disability. As with the Pakistani family,
first cousin marriages in these families carrying the mutations
increased the likelihood of intellectual disability among their
children, and enabled researchers to focus on areas to map genes.

"The combined results from these two studies mean that NSUN2 is among
the most common causes of intellectual disability resulting from
recessive genes," says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene
from each parent to develop intellectual disability. This gene, located
on chromosome 5p, encodes a type of protein called an RNA
methyltransferase.

At the cellular level, the researchers found that the mutated protein
was prevented from reaching its target area within the nucleus of a
cell. As a result, it was unable to perform its normal role in cell
division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in
Cambridge, U.K., showed which type of brain cells were likely to be
most affected by this mutation. They are called Purkinje cells, a type
of neuron that responds to the neurotransmitter GABA. Purkinje cells
also control motor coordination, which were affected in the Pakistani
family.

"We speculate that the muscle effects may result from the accumulation
of the NSUN2 protein outside its target area in the nucleus," says Dr.
Vincent.

To date, Dr. Vincent's lab has identified five genes causing different
forms of recessive intellectual disability.

This research was supported by grants from Pakistan's Higher Education
Commission and the Canadian Institutes of Health Research.

The Centre for Addiction and Mental Health (CAMH) is Canada's largest
mental health and addiction teaching hospital, as well as one of the
world's leading research centres in the area of addiction and mental
health. CAMH combines clinical care, research, education, policy
development and health promotion to help transform the lives of people
affected by mental health and addiction issues.

CAMH is fully affiliated with the University of Toronto, and is a Pan
American Health Organization/World Health Organization Collaborating
Centre.